The goal of this project is to analyze by recombinant DNA techniques sequence transpositions and alterations in gene structure and expression which result from chemical and physical toxic/carcinogenic agents. Molecular clones of "transposon-like" endogenous ecotropic viral genomes of BALB/c and RFM/Un mice have been constructed and characterized. Subgenomic regions have been subcloned to provide molecular probes to specifically detect the ecotropic provirus and any long terminal repeat (LTR) containing genetic regulatory elements. Analysis of spleen DNA of RFM animals with myeloid leukemias and reticulum cell sarcomas has revealed copies of endogenous provirus at new locations in the mouse genome. Replication of the RFM endogenous ecotropic viruses is strongly restricted and the novel integration identified may be due to an intracellular transposition mechanism. Fragment exchange experiments have been done with infectious endogenous and exogenous retroviral genomes to determine the mechanism by which the RFM mouse restricts the endogenous provirus. The results indicate an involvement of the viral gag gene region, possibly by an Fv-1 mechanism.